This research project is designed to provide basic stereochemical knowledge on the three-dimensional molecular structures of biologically significant mono and polyphosphates. Conclusions concerning the chemical bonds, the charge distributions within molecules, the preferred conformations, the inter- and the intra-molecular interactions, etc. can be drawn from the details of the crystal structure. This information is of value in elucidating the mechanism of action or the structural arrangements of these compounds in their biological environments. The specific categories of compounds under investigation comprise phospholipids and polyphosphate cofactors. Single-crystal x-ray diffraction techniques will be used to determine the crystal and molecular structures of interest. Several thiamine analogues and substrate adducts will be investigated, and their features will be analyzed with regard to the biocatalytic role of cocarboxylase. Inositol and its phosphate derivatives will be studied with the objective of establishing a connection between variations in membrane properties and conformational changes in inositol polyphosphates which, in turn, may be due to fluctuations in the nature of the ionic environment. The compounds selected for study provide a representative sampling of the intermolecular associations expected to occur during ion transport. The interactions between local anesthetics and phosphodiesters will be investigated, since the polar heads of phospholipids have been suggested as membrane binding sites for the drugs. The possibility that local anesthetics form complexes with catechol amines will be examined also.